Dopamine vs Noradrenaline: Inverted-U Effects and ADHD Theories

School of Psychiatry, University of New South Wales,, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Australian and New Zealand Journal of Psychiatry (Impact Factor: 3.41). 03/2009; 43(2):101-8. DOI: 10.1080/00048670802607238
Source: PubMed


The aim of the present study was to review the dopamine theory of attention-deficit-hyperactivity disorder (ADHD), in light of recent use of noradrenergic therapies. A historical review of pharmacological theories of ADHD was conducted, including inverted-U, spatial working memory and neural circuit aspects. Pharmacological advances, including animal and human studies of dopaminergic and noradrenergic mechanisms at the prefrontal cortex (PFC), indicate that alpha-2A adrenoreceptor stimulation results in increased dendritic firing during delay periods for preferred directions, while moderate levels of D1 receptor stimulation result in reduction of delay-related firing to non-preferred directions, allowing representational control in the PFC. Recent studies of the COMT val/met gene and stimulant medication response may help explain variation in inverted-U responses in individuals. Further studies utilizing delay-related firing paradigms should be useful in the investigation of attentional syndromes, and responses to newer pharmacological treatments.

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    • "Moreover, decreased working memory (e.g. SWM) (Barkley, 1997; Gallagher and Blader, 2001; McLean et al., 2004; Dowson et al., 2004; Rodriguez-Jimenez et al., 2006; Levy, 2009) and difficulties in executive functioning (Seidman et al., 1998; Mercugliano, 1999; McLean et al., 2004; Rodriguez-Jimenez et al., 2006; Greene et al., 2008) are often reported. At a neurobiological level, due to the ameliorating effect of stimulant medications (e.g. "
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    Psychiatry Research 09/2012; DOI:10.1016/j.psychres.2012.08.013 · 2.47 Impact Factor
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    • "Indeed, prolactin levels were decreased between 60 and 240 min after methylphenidate administration in this group of participants (Linssen et al. 2011). Most studies into effects of dopaminergic drugs on aspects of cognitive performance describe results according to an inverted U curve when performance is mapped as a function of degree of neurotransmitter activity (Levy 2009; Mehta et al. 2004). The design of the present study, using "
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    ABSTRACT: Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate. In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers. In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40 mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test. Declarative memory consolidation was significantly improved relative to placebo after 20 and 40 mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning. To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition.
    Psychopharmacology 12/2011; 221(4):611-9. DOI:10.1007/s00213-011-2605-9 · 3.88 Impact Factor
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    • "Research on ADH) has been published at an exponential rate during the past 30 years [19]. Within the past 3 years (2008 onwards), theories about the etiology of ADHD and therapies for it have evolved concurrently [20-23]. Psychopharmacological agents affecting catecholaminergic and α-2-adrenergic transmission continue to figure prominently in ADHD treatment [24,25]. "
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